The persistent nature of drug seeking and the tendency to relapse are defining features of drug abuse. Cues associated with using drugs are thought to play a critical role in the persistence of drug seeking and in relapse. Drug seeking and taking are operant behavior and animal models of drug self-administration based on the principles of operant conditioning have been useful for studying drug seeking and relapse. Thus, developments in the study of the persistence of operant behavior may provide insights into the persistence of drug-maintained behavior and relapse. Behavioral momentum theory has provided a set of methods and a quantitative theory of how reinforcement conditions affect the persistence of operant behavior in the presence of a stimulus. Based on a prediction of behavioral momentum theory, we have found that the persistence of alcohol seeking in the presence of a stimulus depends on all the reinforcers (both drug and non-drug) available in the presence of that stimulus, even if some of those reinforcers interfere with alcohol seeking. Thus, it may be necessary to consider all of the sources of reinforcement (i.e., drug and non-drug) associated with a drug cue to understand the impact of that cue on the persistence of drug seeking during and after treatment. Extensions of the methods and quantitative theoretical framework of behavioral momentum theory to intravenous cocaine self-administration may provide insights into the persistence of drug seeking in the presence of drug cues. Recently, our laboratory has implemented intravenous cocaine self-administration procedures with rats. The purpose of this R21 Exploratory Developmental Grant is to further develop intravenous cocaine self-administration with rats in our laboratory and to extend behavioral momentum methods and theorizing to cocaine self- administration. The proposed research will examine how the conditions of reinforcement in the presence of cocaine cues contribute to the persistence of cocaine seeking and likelihood of relapse in their presence. Examination of these issues is important because the persistence of drug seeking is a defining feature of drug abuse. The further development of the methods proposed here may provide additional tools that could be useful for identifying genetic and environmental contributions to addictive disorders within animal models. A more formal understanding of how drug cues impact the persistence of drug seeking and relapse may also suggest novel behavioral and pharmacological interventions targeted at reducing the impact of exposure to such cues. PUBLIC HEALTH RELEVANCE: This project is important to public health because it will contribute to our understanding of how drug and non-drug rewards make drug abuse so persistent and likely to relapse. Findings from this project may suggest novel behavioral treatments targeted at reducing the persistence of drug abuse and preventing relapse.